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  2. 2. MELANOMA • Incidence is increasing • Lifetime probability of developing melanoma • 1/37 men • 1/56 women • Five-year survival rates depend upon the stage of the disease at the time of diagnosis • Rare in children and adolescents
  3. 3. RISK FACTORS • Genotype • Personal history of skin cancer • Family history • Atypical nevi • Common nevi • Phenotype • Sun exposure click
  4. 4. SUN EXPOURE • Higher rates with extensive or repeated intense exposure to sunlight • Greater penetration of UV light into the skin results in a higher risk • Incidence is highest in equatorial areas and decreases proportionately with distance from the equator
  5. 5. • Decrease in recreational sun exposure following the diagnosis of primary melanoma, can significantly diminish the chance of a second primary melanoma
  6. 6. • UV-A versus UV-B irradiation • UV-A 320-400 nm • UV-B 290-320 nm • PUVA therapy (Psoralen) • Late increase in the risk of melanoma
  7. 7. TIMING AND PATTERN OF SUN EXPOSURE • Nonmelanoma cancers are associated with cumulative sun exposure • Melanomas are associated with intense, intermittent sun exposure and sunburns
  8. 8. • Tanning beds (since 1920) • Deep tan – status symbol • WHO (2009) UV-A from tanning beds as human carcinogen
  9. 9. CLINICAL FEATURES • Superficial tumors that are confined to the epidermis • Horizontal or "radial" growth phase • “Vertical" growth phase
  10. 10. • Subtypes • Superficial spreading • Nodular • Lentigo maligna melanoma • Acral lentiginous melanoma
  11. 11. SUPERFICIAL SPREADING MELANOMA • The most common subtype • Over 60% are diagnosed as thin, highly curable tumors of less than 1 mm thickness • Can occur in any anatomic location • Variably pigmented macule or plaque with an irregular border, ranging from a few millimeters to several centimeters in diameter
  12. 12. • Multiple shades of red, tan, brown, blue, black, gray, and white can be appreciated • Histologically • Asymmetric, poorly circumscribed, lack cellular maturation
  13. 13. • In the radial phase of growth, there is haphazard growth of neoplastic melanocytes with single-cell spread throughout the layers of the epidermis • Transition to vertical growth phase occurs when the largest nest in the dermis exceeds that in the epidermis
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  15. 15. NODULAR MELANOMA • Vertical growth phase melanomas • 15 to 30 percent of all melanomas • Darkly pigmented, pedunculated or polypoid nodule • Histologically • Dermal growth occurs in isolation or, occasionally • Neoplastic cells within the dermal growth may appear epithelioid or spindled • Mitoses are frequent and often atypical
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  17. 17. LENTIGO MALIGNA MELANOMA • Most commonly arises in sun-damaged areas of the skin in older individuals • Begins as a freckle-like tan-brown macule • Transformation is slow • Once it is fully evolved, color variegation can be striking
  18. 18. • Histologically • During the radial growth phase, the atypical melanocytes are usually polygonal in shape with hyperchromatic, angulated nuclei • Multinucleated giant melanocytes ("star-burst giant cells") may be present at the basal layer of the epidermis • The hallmark of the vertical growth phase is the formation of dermal nodules and fascicles that are larger than the epidermal component • Pleomorphic with variably hyperchromatic nuclei
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  20. 20. ACRAL LENTIGINOUS MELANOMA • The least common variant of radial growth phase melanomas • Fewer than 5 percent of all melanomas • Palmar, plantar, subungual, and occasionally, mucosal surfaces • Most common type of malignant melanoma among asians and dark-skinned individuals • Not all melanomas arising in acral sites are acral lentiginous melanomas
  21. 21. • Dark brown to black, unevenly pigmented patch • Areas of regression manifest as foci of gray-white discoloration
  22. 22. • Histologically • Lentiginous array of atypical melanocytes along the dermal- epidermal junction, with foci of confluent melanocytic growth • Invasive lesions are characterized by the presence of neoplastic single cells or nests in the dermis • Large, hyperchromatic, angulated melanocytes with scant cytoplasm
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  24. 24. DIAGNOSIS • The clinical recognition of melanoma may be challenging even for the most experienced dermatologist • Asymmetry • Irregular borders • Variegated color • Diameter >6mm • Recent change in a lesion
  25. 25. ABCDE RULE • Asymmetry (if a lesion is bisected, one half is not identical to the other half) • Border irregularities • Color variegation (brown, red, black or blue/gray, and white) • Diameter ≥6 mm • Evolving: a lesion that is changing in size, shape, or color, or a new lesion
  26. 26. THE REVISED GLASGOW SEVEN-POINT CHECKLIST • Major: • Change in size/new lesion • Change in shape • Change in color • Minor: • Diameter ≥7mm • Inflammation • Crusting or bleeding • Sensory change
  27. 27. THE "UGLY DUCKLING" SIGN • A pigmented lesion that looks different from other surrounding lesions must be considered suspicious, even if it does not fulfill the ABCD criteria.
  28. 28. DIFFERENTIAL DIAGNOSIS • Common melanocytic nevus • Atypical melanocytic nevus • Traumatized nevus • Blue nevus • Lentigo (ink spot) • Spitz nevus • Melanonychia striata
  29. 29. • Pigmented basal cell carcinoma • Pigmented actinic keratosis • Seborrheic keratosis • Pyogenic granuloma • Cherry hemangioma • Dermatofibroma • Keratoacanthoma • Subungual hematoma
  31. 31. • Referral • A new mole appearing after the onset of puberty which is changing in shape, color, or size • A long-standing mole which is changing in shape, color, or size • Any mole which has three or more colors or has lost its symmetry • A mole which is itching or bleeding • Any new persistent skin lesion especially if growing, if pigmented or vascular in appearance, and if the diagnosis is not clear • A new pigmented line in a nail especially where there is associated damage to the nail • A lesion growing under a nail
  32. 32. • Biopsy • Biopsy is necessary whenever melanoma is suspected. • An excisional biopsy that includes the entire lesion with 1 to 3 mm margins of normal skin and part of the subcutaneous fat should be performed whenever possible. • Incisional biopsy may be occasionally acceptable for very large lesions or for certain sites, including the face, palm or sole, ear, distal digit, or subungual lesions
  33. 33. • Monitoring • Patients at increased risk of melanoma should have regular examinations once or twice a year • Australian Cancer Network recommends monthly skin self- examination and biannual full body skin examination by a clinician for high risk individuals
  35. 35. PROGNOSTIC FACTORS • Primary tumor (T) • Tumor thickness • Mitotic rate • Ulceration • Lymphatic involvement (N) • Node classification • Satellite lesions and in transit metastases • Distant metastases (M) • Age • Gender • Anatomic
  36. 36. MANAGEMENT
  37. 37. INITIAL BIOPSY • Excisional biopsy • Incisional biopsy • Shave biopsy • Never appropriate for the following reasons • The lesion is likely to be inadequately excised, with residual tumor remaining at both the radial and deep margins. • Because only the superficial portion of the tumor is removed, shave biopsies results underestimate tumor thickness, a critical prognostic factor and determinant of treatment. • Fibrosis and scarring at the base of the biopsy site may obscure residual melanoma, making it impossible for a pathologist to identify tumor and accurately measure its thickness.
  38. 38. WIDE LOCAL EXCISION • The definitive surgical treatment • The recommended width of the normal tissue around the lesion has progressively decreased as a result of multiple large clinical trials that have examined the impact of the surgical margin on the local recurrence rate • The thickness of the melanoma is a key factor in determining the stage of the lesion and the recommended margin of normal tissue to be resected.
  39. 39. Study, author; year n Median follow-up Melanoma thickness Margi ns Local recurrence, (percent) Overall survival, percent World Health Organization Cascinelli, N; 1998 612 12 yrs 0-1 mm 1 cm 3/186 (1.6) 87 1.1-2 mm 1 cm 5/119 (4.2) 0-1 mm 3 cm 1/173 (0.6) 85 1.1-2 mm 3 cm 2/134 (1.5) Swedish Cohn-Cedarmark, G; 2000 989 11 yrs 0.8-2 mm 2 cm 3/476 (0.6) 79 5 cm 5/513 (1) 76 French Cooperative Group Khayat, D; 2003 326 16 yrs <2.1 mm 2 cm 1/181 (0.05) 87 5 cm 4/185 (0.2) 86 Melanoma Intergroup Trial Karakoussis, CP; 1996 468 8 yrs 1-4 mm 2 cm (2.1) 80 4 cm (2.6) 84 British Trial Thomas, JM; 2004 900 60 mos ≥2 mm 1 cm 15/453 (3.3) No significant difference3 cm 13/457 (2.8)
  40. 40. WIDE LOCAL EXCISION • Thin melanomas • Resect melanomas <1 mm thick (T1) with a 1 cm margin of normal tissue • For melanomas 1 to 2 mm thick (T2 lesions), use a 2 cm margin of normal tissue if this is feasible without the need for a skin graft
  41. 41. • Intermediate thickness melanomas • Primary melanomas between 2 and 4 mm thick (T3), 2 cm excision margin
  42. 42. • Thick melanomas • Thick melanomas (ie, those >4 mm), 2cm excision margin
  43. 43. • In situ melanomas • There are no data from randomized trials to define the optimal extent of surgical resection. • Retrospective data support the routine use of 0.5 cm margins
  44. 44. LYMPH NODE METASTASIS • 20 percent of clinically node-negative patients have metastatic involvement • 20 percent of those with clinically positive nodes are pathologically negative
  45. 45. CLINICALLY APPARENT REGIONAL LYMPH NODES • Therapeutic lymphadenectomy • Elective lymph node dissection • Sentinel lymph node biopsy
  46. 46. THERAPEUTIC LYMPHADENECTOMY • Therapeutic lymphadenectomy is the preferred treatment for cytologically or pathologically proven regional lymph node involvement • Complete regional lymphadenectomy is necessary rather than partial dissection or sampling
  47. 47. ELECTIVE LYMPH NODE DISSECTION • ELND for clinically node-negative patients is controversial despite a number of trials evaluating this approach • There may be subgroups of patients who benefit from ELND, but consensus is lacking on this issue.
  48. 48. SENTINEL LYMPH NODE BIOPSY • If the sentinel lymph nodes are not involved, the entire basin should be free of tumor • Completion lymph node dissection is used for patients with tumor involvement of the sentinel lymph node
  49. 49. • Patient selection • SLNB is indicated for tumors ≥1 mm thick. • Tumors less than 1 mm in thickness have less than a 10 percent likelihood of nodal metastases, and SLNB is not routinely indicated. However, certain high-risk features (ulceration, a mitotic rate ≥1 per mm2) are associated with a higher rate of lymph node metastasis, thereby justifying the use of SLNB • Tumors >4 mm thick have a 65 to 70 percent risk of distant metastasis. However, SLNB may still provide important prognostic information.
  50. 50. SURVEILLANCE AFTER TREATMENT • The primary objective of follow-up in patients with melanoma is to identify potentially curable locoregional recurrences and second primary cancers.
  51. 51. • A routine physical examination, including a full skin assessment and palpation of the regional lymph nodes, which should be repeated at least yearly • The frequency of such evaluation should be increased in patients at high risk of recurrence • Imaging studies should be done if symptoms are present; the value of routine imaging is uncertain